Methods for treating malignant tumors may be generally classified into surgical methods, chemotherapy and radiotherapy (radiation therapy). About 35% of all cancer patients in South-Korea and about 50% thereof in US receive some type of radiotherapy, at present, and the number of domestic patients who need to receive radiotherapy is increasing every year. Under this circumstance, the importance of radiotherapy in cancer treatment is presently increasing. Radiotherapy has been known as an essential treatment method for various types of cancer, however, it also has some problems such as resistance to radiation built in cancer cells, low efficiency against solid cancers, damages in normal tissue when high-dose of radiation is applied, or the like, resulting in lowering the efficiency in cancer treatment. For obtaining high anti-tumor effect, chemoradiotherapy, i.e., the combined therapy simultaneously using chemotherapy agents and radiation, has been introduced as a general therapy, and it has also been reported that it gives better results than chemotherapy or radiotherapy alone (Nishimura, Y., Int. J. Clin. Oncol., 2004, 9, 414). It was reported, for instance that in head and neck cancer, the combination of carboplatin/fluorouracil and radiation treatment (Calais et al., J. Natl. Cancer Inst. 1999, 91, 2081) and another combination of cisplatin and radiation treatment (Jeremic et al., J. Clin. Oncol. 2000, 18, 1458), and the combination of fluorouracil and radiation treatment in pancreatic cancer (Moertel, et al., Cancer 1981, 48, 1705) etc. significantly extended the surviving period in patients, as compared when radiotherapy was applied alone.
Many approaches to develop radiosensitizers that can reduce the radiation dose so as to reduce side effects without decreasing the efficacy of radiotherapy have been made. For example, compounds such as misonidazole and etanidazole, etc. were developed from nitroimidazole derivatives which are known as a radiosensitizer. However, these compounds were not successfully commercialized for practical use due to the fact that they have strong neurotoxicity when used at the effective amount for radiosensitizing effect.